title: Down-regulation of TRPM8 in pulmonary arteries of pulmonary hypertensive rats.
abstract: BACKGROUND
  Pulmonary hypertension (PH) is characterized by profound vascular remodeling and alterations in Ca(2+) homeostasis in pulmonary arterial smooth muscle cells (PASMCs). Multiple transient receptor potential melastatin-related (TRPM) subtypes have been identified in vascular tissue. However, the changes in the expression and function of TRPM channels in pulmonary hypertension have not been characterized in detail.
  
  
  METHODS
  We examined the expression of TRPM channels and characterized the functions of the altered TRPM channels in two widely used rat models of chronic hypoxia (CH)- and monocrotaline (MCT)-induced PH.
  
  
  RESULTS
  CH-exposed and MCT-treated rats developed severe PH and right ventricular hypertrophy, with a significant decrease in TRPM8 mRNA and protein expression in pulmonary arteries (PAs). The downregulation of TRPM8 was associated with significant reduction in menthol-induced cation-influx. Time-profiles showed that TRPM8 down-regulation occurred prior to the increase of right ventricular systolic pressure (RVSP) and right ventricular mass index (RVMI) in CH-exposed rats, but these changes were delayed in MCT-treated rats. The TRPM8 agonist menthol induced vasorelaxation in phenylephrine-precontracted PAs, and the vasorelaxing effects were significantly attenuated in PAs of both PH rat models, consistent with decreased TRPM8 expression.
  
  
  CONCLUSIONS
  Downregulation of TRPM8 may contribute to the enhanced vasoreactivity in PH.
authors.affiliation: Department of Physiology and Pathophysiology, Fujian Medical University, Fuzhou, Fujian Province, People's Republic of China.
authors.forename: Xiao-Ru
authors.initials: XR
authors.lastname: Liu
authors.forename: Qing
authors.initials: Q
authors.lastname: Liu
authors.forename: Gai-Ying
authors.initials: GY
authors.lastname: Chen
authors.forename: Ying
authors.initials: Y
authors.lastname: Hu
authors.forename: James S K
authors.initials: JS
authors.lastname: Sham
authors.forename: Mo-Jun
authors.initials: MJ
authors.lastname: Lin
mesh_terms: D000818:Animals; D002412:Cations / Q000378:metabolism; D015536:Down-Regulation / Q000187:drug effects; D016257:Fura-2 / Q000737:chemistry; D006976:Hypertension, Pulmonary / Q000139:chemically induced / Q000209:etiology / Q000378:metabolism*; D017380:Hypertrophy, Right Ventricular / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology; D000860:Hypoxia; D008168:Lung / Q000098:blood supply; D008297:Male; D008345:Manganese / Q000378:metabolism; D008610:Menthol / Q000494:pharmacology; D016686:Monocrotaline / Q000633:toxicity; D011651:Pulmonary Artery / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D050053:TRPM Cation Channels / Q000819:agonists / Q000235:genetics / Q000378:metabolism*; D014664:Vasodilation / Q000187:drug effects
chemical_list: D002412:Cations; D050053:TRPM Cation Channels; C498947:Trpm8 protein, rat; D008610:Menthol; D008345:Manganese; D016686:Monocrotaline; D016257:Fura-2